A new retrospective study published on October 23, 2026, in Advances in Radiation Oncology reports that incorporating intentional intratumoral hotspots into volumetric modulated arc therapy (VMAT)-based stereotactic body radiation therapy (SBRT) may significantly reduce local recurrence in patients with early-stage non-small cell lung cancer (NSCLC).
The study, titled “Adding SPICE to SBRT: Clinical Outcomes with Intentional Hotspot Design After VMAT SBRT for Early-Stage NSCLC,” was conducted by Bryan A. Johnson, Bradford S. Hoppe, and colleagues. It evaluated whether deliberately increasing the maximum dose within the treatment target to at least 120% of the prescribed dose could improve local tumor control compared with more homogeneous radiation dose distributions.
Among 140 patients treated for 149 lung lesions, the investigators observed no local recurrences in patients receiving treatment plans with a maximum planning target volume (PTV) dose of at least 120%, compared with a 3-year cumulative local recurrence incidence of 8.4% among patients treated with lower maximum doses.
The findings raise an important question for contemporary radiation treatment planning: could intentional dose heterogeneity within the tumor improve the effectiveness of SBRT without compromising its established precision?
Beyond Uniform Dose Distribution: Rethinking SBRT Planning
Stereotactic body radiation therapy is an established treatment option for medically inoperable patients with early-stage NSCLC, offering high rates of local tumor control through the delivery of ablative radiation doses over a limited number of fractions.
Historically, SBRT techniques using three-dimensional conformal radiotherapy and dynamic conformal arc therapy produced heterogeneous dose distributions, frequently resulting in higher radiation doses within the tumor.
The introduction of VMAT has provided greater flexibility in treatment planning, allowing highly conformal dose delivery, improved sparing of surrounding normal tissues, and more homogeneous dose distributions across the target.
However, increasing dose uniformity may not necessarily represent the optimal approach to maximizing tumor control.
Previous clinical investigations and radiobiological modeling have suggested that higher intratumoral doses, particularly maximum doses reaching or exceeding 120% of the prescription, may be associated with improved local control.
Nevertheless, differences in dose prescription practices, treatment planning techniques, and reporting standards have complicated efforts to establish the clinical significance of intentional hotspots.
Against this background, the investigators examined whether incorporating a deliberately designed intratumoral hotspot into VMAT SBRT plans could influence local recurrence in patients with early-stage NSCLC.
Inside the Study: 140 Patients and 149 Lung Lesions
The single-institution retrospective analysis included 140 patients with stage I or node-negative stage II NSCLC who underwent VMAT SBRT between April 2017 and January 2024.
A total of 149 lesions were treated, including seven patients with two lesions and one patient with three lesions.
Patients were divided into two groups according to the maximum dose delivered to the planning target volume:
- Hotspot ≥120%: 54 patients and 60 treated lesions, with a PTV maximum dose reaching at least 120% of the prescribed dose.
- Hotspot <120%: 86 patients and 89 treated lesions, with a PTV maximum dose below 120% of the prescription.
Treatment regimens consisted of either 48 Gy in four fractions or 50 Gy in five fractions.
All treatments were delivered using a Varian TrueBeam linear accelerator with flattening-filter-free 6 MV or 10 MV photon beams. Treatment planning generally incorporated two partial VMAT arcs to maintain target coverage while limiting radiation exposure to surrounding organs at risk.
The planning objective required at least 95% of the PTV to receive 95% of the prescribed dose, a threshold achieved in 138 of the 149 treatments.
The primary endpoint was local recurrence, evaluated through both patient-level and lesion-level analyses while accounting for death as a competing risk. Progression-free survival (PFS) and overall survival (OS) were assessed as secondary endpoints.
Median follow-up was 2.7 years.
A Significant Difference in Local Recurrence
The most notable finding was the difference in local recurrence between patients treated with and without intentional high-dose hotspots.
Across the entire cohort, 10 patients (7.1%) experienced local recurrence, corresponding to 11 treated lesions (7.4%).
All local recurrences occurred in the Hotspot <120% group.
At three years, the cumulative incidence of local recurrence in the patient-level analysis was:
- 0% in the Hotspot ≥120% group.
- 8.4% in the Hotspot <120% group.
The difference was statistically significant (P = .022).
The findings remained significant after adjustment for American Joint Committee on Cancer (AJCC) stage (P = .045).
A similar association was observed in the lesion-level analysis, where the 3-year cumulative incidence of local recurrence was 0% in the Hotspot ≥120% group compared with 9.3% in the Hotspot <120% group (P = .012).
After adjustment for AJCC stage, this difference also remained statistically significant (P = .025).
Of the 11 local recurrences, 10 occurred within the original treatment’s 100% prescription isodose line, while the remaining recurrence overlapped the 80% isodose line.
The median time to local recurrence was 1.3 years.
These findings suggest that the maximum dose delivered within the target may represent an important dosimetric factor influencing local tumor control following VMAT SBRT.
Local Control Improved, but Survival Outcomes Remained Unchanged
Despite the significant differences in local recurrence, the investigators did not identify statistically significant improvements in progression-free or overall survival between the two treatment groups.
Across the entire study population, progression-free survival was:
- 79.7% at one year.
- 64.8% at two years.
- 52.1% at three years.
Overall survival was:
- 92.0% at one year.
- 78.6% at two years.
- 64.4% at three years.
After adjustment for AJCC stage, the hazard ratio for progression-free survival was 0.94 (95% CI, 0.57–1.55; P = .80), while the corresponding hazard ratio for overall survival was 0.80 (95% CI, 0.45–1.45; P = .47).
The absence of a significant survival difference indicates that improved local tumor control did not translate into a demonstrated survival advantage within the available follow-up period.
The investigators also reported that 62 patients (44.3%) died during follow-up. Among those who died, 13.8% of deaths were attributed to lung cancer, 58.5% to other causes, and 27.7% to unknown causes.
These findings emphasize the importance of distinguishing local treatment effectiveness from broader survival outcomes in patients with early-stage NSCLC, particularly in populations with substantial comorbidities and competing mortality risks.
Introducing SPICE: A Structured Approach to Intentional Dose Escalation
An important component of the study is the description of the institution’s evolving treatment planning approach, known as SPICE (Stereotactic Planning with Intentional Central Escalation).
The SPICE methodology was developed to standardize the location and magnitude of intentional hotspots while maintaining normal tissue dose constraints.
Under this approach, an internal gross tumor volume (IGTV) is generated to account for respiratory-induced tumor motion.
Nearby organs at risk are expanded, typically by 3 mm in the thorax, to create planning risk volumes (PRVs).
These volumes are subsequently subtracted from the IGTV to establish a definitive target volume (DTV), which serves as the preferred region for intentional dose escalation.
The investigators describe two implementations of this planning strategy.
Regular SPICE incorporates a localized hotspot within the DTV, targeting a maximum dose of at least 120% but less than 150% of the prescription.
Extra SPICE aims to deliver at least 120% of the prescribed dose throughout the entire DTV while maintaining strict dose limitations for adjacent organs at risk. Dose within overlapping OAR/PTV regions is constrained to no more than 105% of the prescription and must remain below organ-specific maximum limits.
The selection of approach depends on tumor location and the relationship between the target and surrounding critical structures.
This methodology seeks to preserve the conformality and organ-sparing advantages of VMAT while deliberately incorporating intratumoral dose heterogeneity.
Why Might Higher Intratumoral Doses Improve Tumor Control?
The potential biological benefits of intentional hotspots remain an area of investigation.
One proposed explanation involves spatial variations in tumor perfusion, oxygenation, and radiation sensitivity.
Tumors frequently contain heterogeneous microenvironments, including regions with differing levels of hypoxia and treatment resistance. Delivering higher radiation doses to selected intratumoral regions may improve the probability of eliminating resistant malignant cell populations.
The investigators also discuss possible contributions from radiation-induced bystander and abscopal-like effects, through which irradiation of one tumor region may influence neighboring malignant cells.
Although these mechanisms remain hypothetical in this setting, they provide a biological rationale for investigating nonuniform dose distributions.
The study’s findings are consistent with previous modeling and clinical investigations suggesting associations between higher biologically effective doses, intratumoral dose escalation, and improved local tumor control.
Interpreting the Evidence: Important Limitations
Although the results demonstrate a statistically significant association between intentional hotspots and reduced local recurrence, several limitations must be considered.
The retrospective, single-institution design introduces the possibility of selection bias and unmeasured confounding.
The study population was relatively small, and the treatment groups differed in disease stage. Patients receiving plans with maximum doses below 120% had a greater proportion of stage IB and stage IIA–IIB disease.
Additionally, the Hotspot ≥120% group had a shorter median follow-up period of 2.6 years compared with 3.3 years in the Hotspot <120% group.
This difference reflected the institution’s increasing adoption of intentional hotspot planning during the later years of the study.
Although the investigators performed stage-adjusted analyses, residual confounding cannot be excluded.
The absence of local recurrence in the higher-hotspot group is encouraging, but it does not establish that a 120% hotspot eliminates recurrence risk or that the same results would be reproduced in larger patient populations.
The study also did not establish an optimal hotspot magnitude or determine whether escalation to 115%, 120%, 130%, or higher levels would provide the greatest clinical benefit.
Prospective investigations with standardized dosimetric reporting and longer follow-up will therefore be necessary before intentional hotspot incorporation can be recommended as a routine VMAT SBRT planning objective.
What Comes Next for VMAT SBRT in Early-Stage NSCLC?
The findings contribute to an ongoing discussion regarding the importance of intratumoral dose distribution in stereotactic radiation treatment planning.
While contemporary VMAT techniques provide excellent conformity and normal tissue sparing, the results suggest that maximizing dose homogeneity may not always be necessary to achieve optimal local control.
The investigators propose further evaluation of hotspot magnitude, spatial distribution, target coverage, fractionation, respiratory motion management, and adjacent organ-at-risk protection.
Standardized reporting of maximum PTV dose and high-dose subvolumes, including V120% within the IGTV or DTV, may also improve comparisons between treatment approaches.
For radiation oncologists and medical physicists, the study highlights the potential clinical relevance of treatment plan characteristics beyond conventional prescription dose and target coverage metrics.
The central finding is that VMAT SBRT plans incorporating a PTV maximum dose of at least 120% were associated with significantly lower local recurrence in early-stage, node-negative NSCLC, without a demonstrated difference in progression-free or overall survival.
Although prospective validation remains necessary, the SPICE approach offers a structured framework for investigating intentional intratumoral dose escalation while respecting normal tissue constraints.
The study reinforces the importance of considering not only how much radiation is prescribed, but also how that dose is distributed within the tumor.
Original Research
Johnson BA, Hoppe BS, Fang ZJ, et al. Adding SPICE to SBRT: Clinical Outcomes with Intentional Hotspot Design After VMAT SBRT for Early-Stage NSCLC. Advances in Radiation Oncology. Published online October 23, 2026. Article 102245.
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